(17-11-2017) Endocrine regulation of male fertility by the skeleton

Franck Oury,1,* Grzegorz Sumara,1,* Olga Sumara,1 Mathieu Ferron,1 Haixin Chang,2 Charles E. Smith,3 Louis Hermo,3 Susan Suarez,2 Bryan L. Roth,4 Patricia Ducy,5 and Gerard Karsenty1,‡
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Abstract

Although the endocrine capacity of bone is widely recognized, interactions between bone and the reproductive system have until now focused on the gonads as a regulator of bone remodeling. We now show that in males, bone acts as a regulator of fertility. Using co-culture assays, we demonstrate that osteoblasts are able to induce testosterone production by the testes, while they fail to influence estrogen production by the ovaries. Analyses of cell-specific loss- and gain-of-function models reveal that the osteoblast-derived hormone osteocalcin performs this endocrine function. By binding to a G-protein coupled receptor expressed in the Leydig cells of the testes, osteocalcin regulates in a CREB-dependent manner the expression of enzymes required for testosterone synthesis, promoting germ cell survival. This study expands the physiological repertoire of osteocalcin, and provides the first evidence that the skeleton is an endocrine regulator of reproduction.

Source: Cell. 2011 Mar 4; 144(5): 796–809.
Published online 2011 Feb 17. doi: 10.1016/j.cell.2011.02.004
PMCID: PMC3052787
NIHMSID: NIHMS272217

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